Multiple Sclerosis Patient Macrophages Impaired Metabolism Leads to an Altered Response to Activation Stimuli
Abstract
BACKGROUND AND OBJECTIVES: In multiple sclerosis (MS), immune cells invade the CNS and destroy myelin. Macrophages contribute to demyelination and myelin repair, and their role in each process depends on their ability to acquire specific phenotypes in response to external signals. In this article, we assess whether defects in MS patient macrophage responses may lead to increased inflammation or lack of neuroregenerative effects. METHODS: monocytes from patients with MS and healthy controls (HCs) were activated in vitro to obtain homeostatic-like, proinflammatory, and proregenerative macrophages. Macrophage activation profiles were assessed through RNA sequencing and metabolomics. Surface molecule expression of CD14, CD16, and HLA-DR and myelin phagocytic capacity were evaluated with flow cytometry. Macrophage supernatant capacity to influence oligodendrocyte precursor cell differentiation toward an astrocytic or oligodendroglia fate was also tested. RESULTS: phenotype, a subset of proinflammatory cells overrepresented in MS lesions. Functionally, MS patient macrophages display a decreased capacity to phagocytose human myelin and a deficit of processing myelin after ingestion. In addition, MS patient macrophage supernatant favors astrocytes over oligodendrocyte differentiation when compared with HC macrophage supernatant. Furthermore, even when exposed to homeostatic or proregenerative stimuli, MS patient macrophages uphold a proinflammatory transcriptomic profile with higher levels of cytokine/chemokine. Of interest, MS patient macrophages exhibit a distinct metabolic signature with a mitochondrial energy metabolism blockage. Transcriptomic data are further substantiated by metabolomics studies that reveal perturbations in the corresponding metabolic pathways. DISCUSSION: Our results show an intrinsic defect of MS patient macrophages, reminiscent of innate immune cell memory in MS, lifting macrophage importance in the disease and as potential therapeutic targets.
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BibTeX
@article{fransson2026multiple,
title = {{Multiple Sclerosis Patient Macrophages Impaired Metabolism Leads to an Altered Response to Activation Stimuli}},
author = {Jennifer Fransson and Corinne Bachelin and Farid Ichou and Léna Guillot-Noël and Maharajah Ponnaiah and Arnaud Gloaguen and Elisabeth Maillart and Bruno Stankoff and Arthur Tenenhaus and Bertrand Fontaine and Fanny Mochel and Celine Louapre and Violetta Zujovic},
journal = {Neurology Neuroimmunology \& Neuroinflammation},
year = {2026},
month = sep,
doi = {10.1212/nxi.0000000000200312},
url = {https://hal.science/hal-05772317v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Multiple Sclerosis Patient Macrophages Impaired Metabolism Leads to an Altered Response to Activation Stimuli
AU - Jennifer Fransson
AU - Corinne Bachelin
AU - Farid Ichou
AU - Léna Guillot-Noël
AU - Maharajah Ponnaiah
AU - Arnaud Gloaguen
AU - Elisabeth Maillart
AU - Bruno Stankoff
AU - Arthur Tenenhaus
AU - Bertrand Fontaine
AU - Fanny Mochel
AU - Celine Louapre
AU - Violetta Zujovic
PY - 2026
DA - 2026/09/30
JO - Neurology Neuroimmunology & Neuroinflammation
DO - 10.1212/nxi.0000000000200312
UR - https://hal.science/hal-05772317v1
AB - BACKGROUND AND OBJECTIVES: In multiple sclerosis (MS), immune cells invade the CNS and destroy myelin. Macrophages contribute to demyelination and myelin repair, and their role in each process depends on their ability to acquire specific phenotypes in response to external signals. In this article, we assess whether defects in MS patient macrophage responses may lead to increased inflammation or lack of neuroregenerative effects. METHODS: monocytes from patients with MS and healthy controls (HCs) were activated in vitro to obtain homeostatic-like, proinflammatory, and proregenerative macrophages. Macrophage activation profiles were assessed through RNA sequencing and metabolomics. Surface molecule expression of CD14, CD16, and HLA-DR and myelin phagocytic capacity were evaluated with flow cytometry. Macrophage supernatant capacity to influence oligodendrocyte precursor cell differentiation toward an astrocytic or oligodendroglia fate was also tested. RESULTS: phenotype, a subset of proinflammatory cells overrepresented in MS lesions. Functionally, MS patient macrophages display a decreased capacity to phagocytose human myelin and a deficit of processing myelin after ingestion. In addition, MS patient macrophage supernatant favors astrocytes over oligodendrocyte differentiation when compared with HC macrophage supernatant. Furthermore, even when exposed to homeostatic or proregenerative stimuli, MS patient macrophages uphold a proinflammatory transcriptomic profile with higher levels of cytokine/chemokine. Of interest, MS patient macrophages exhibit a distinct metabolic signature with a mitochondrial energy metabolism blockage. Transcriptomic data are further substantiated by metabolomics studies that reveal perturbations in the corresponding metabolic pathways. DISCUSSION: Our results show an intrinsic defect of MS patient macrophages, reminiscent of innate immune cell memory in MS, lifting macrophage importance in the disease and as potential therapeutic targets.
SN - 2332-7812
ER -